Adjustment For Traditional Risk Factors Research Articles

Low Serum Dehydroepiandrosterone Is Associated With Diabetic Kidney Disease in Men With Type 2 Diabetes Mellitus.

BackgroundThe associations of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) with diabetic kidney disease (DKD) remained unclear. Thus, this cross-sectional study aimed to explore the associations of DHEA and DHEAS with the risk of DKD in patients with T2DM.MethodsThe information of 1251 patients with T2DM were included in this study. Serum DHEA and DHEAS were quantified using liquid chromatography-tandem mass spectrometry assays. Multivariate logistic regression analyses were used to assess the associations of DHEA and DHEAS with DKD as well as high urine albumin to creatinine ratio (ACR).ResultsIn men with T2DM, the risk of DKD decreased with an increasing DHEA concentration after adjustment for traditional risk factors; the fully adjusted OR (95% CI) for tertile3 vs tertile1 was 0.37 (0.19-0.70; P = 0.010 for trend). Similarly, when taking high ACR as the outcome, low DHEA levels were still significantly associated with increased odds of high ACR (OR, 0.37; 95% CI, 0.19–0.72 for tertile3 vs tertile1; P = 0.012 for trend). The restricted cubic spline showed that the risk of DKD gradually decreased with the increment of serum DHEA levels (P-overall = 0.007; P-nonlinear = 0.161). DHEAS was not independently associated with the risk of DKD in men. In contrast, no significant relationships were found between DHEA and DHEAS and the risk of DKD in women (all P > 0.05).ConclusionsIn men with T2DM, low serum DHEA levels were independently related to the risk of DKD after adjustment for traditional risk factors. Our finding highlights the potential role of DHEA in the development of DKD in men with T2DM.

TIME SERIES CLUSTERING OF LEFT ATRIAL STRAIN CURVES FOR RISK STRATIFICATION IN THE GENERAL POPULATION

Objective: Currently, only the peak reservoir left atrial (LA) strain has been in use while a huge amount of useful information during different phases of cardiac cycle has been ignored. In this study, therefore, we tested the hypothesis that an unsupervised time series analysis utilizing the whole LA deformation curves will identify distinct clusters associated to risk factors and improve cardiovascular (CV) risk prediction over the traditionally used covariables in the general population. Design and method: We prospectively studied 929 community-dwelling individuals (mean age, 51.6 years; 52.9% women), in whom we acquired clinical and echocardiographic data including LA strain traces at baseline and collected cardiac events on average 7.2 years later. We employed two unsupervised time series techniques such as Self-Organizing map and Variational Autoencoder with Convolutional Neural Network as building block to cluster spatiotemporal patterns of LA strain curves. Clinical characteristics and cardiac outcome were used to evaluate the validity of the clusters (k). Results: According to the quantization error value for every k, the optimal number of clusters was 5 for applied methods. Overall, both methods agreed with respect to cluster assignment. Figure (left panel) presents centroid LA strain curves which represent each cluster. The first three clusters had differences in sex distribution and heart rate, but had similar low CV risk profiles. On the other hand, cluster 5 had the worst CV risk factors combination, and higher prevalence of left ventricular remodelling and diastolic dysfunction (ie, lowest e’ velocity and highest E/e’) compared to other clusters. We also observed an increase in the risk for incidence of adverse events between cluster 5 and other clusters (Figure, right panel). After adjustment for traditional risk factors, cluster 5 had the highest risk of cardiac events as compared to cluster 1, 2 and 3 (HR: 1.34; 95%CI: 1.05–1.73); P = 0.020). Conclusions: Unsupervised Machine/Deep Learning algorithms employed on time series LA strain curves identifies clinically meaningful clusters of LA deformation, and provides incremental prognostic information over traditional risk stratification.

Baseline carotid intima-media complex echogenicity associates with the 3-year progression of intima-media thickness

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Region Vasterbotten Central ALF and the Swedish Research Council Background Echogenicity of the intima-media (IM) complex and progression of carotid intima media thickness (cIMT) have both separately been demonstrated to predict cardiovascular disease (CVD). However, it is unknown if the IM echogenicity reflects arterial wall remodelling associated with increased progression of cIMT. Purpose The aim of this study was to evaluate if the baseline echogenicity of the IM-complex measured by ultrasound is associated with cIMT progression over a 3-year follow-up period. Methods Ultrasound images from baseline and 3-year follow-up performed for the randomised controlled trial ‘Visualization of asymptomatic atherosclerotic disease for optimum cardiovascular prevention’ (VIPVIZA) were included in this study (n: 3154). Participants were 40, 50 or 60 years old at baseline and had at minimum one traditional risk factor for CVD to be included in the VIPVIZA study. Measurements of mean cIMT were made at baseline and in the 3-year follow-up in the distal 1 cm of the common carotid artery at standardised angles bilaterally. Echogenicity of the IM-complex was determined by greyscale median (IM-GSM), automatically calculated from the B-mode ultrasound images. Associations between IM-GSM at baseline and the 3-year progression of cIMT were investigated using linear regression models, and stratified by sex, age and VIPVIZA study group (intervention versus control). In addition, adjusted analysis for traditional risk factors was also performed. All analysis was carried out on left and right sides separately. Results The unadjusted analysis showed associations between baseline IM-GSM with the 3-year progression of cIMT (p<0.001 for both left and right sides, Figure 1). The association between IM-GSM and cIMT was statistically significant bilaterally in both male and female participants and on comparison of VIPVIZA study subgroups. When stratifying by age group, the association between baseline IM-GSM and cIMT progression was present among 40 (p<0.001) and 60 year olds (p<0.001), but not among 50 years old (p=0.906) in the left side. In the right CCA the association was significant among 40 years old (p=0.047), but not for 50 and 60 years (p=0.106 and 0.067, respectively). Adjustments for traditional risk factors did not alter the estimated relationship between baseline IM-GSM and 3-year cIMT progression. Conclusion Baseline ultrasound echogenicity of the IM-complex is associated with the 3-year progression of cIMT among a middle-aged population with subclinical atherosclerosis. Echogenicity of the IM-complex may serve to identify arterial wall remodelling reflecting progressive atherosclerotic disease and could be a valuable tool in future CVD prevention.

Association of Non-Alcoholic Fatty Liver Disease and Hepatic Fibrosis with Epicardial Adipose Tissue Volume and Atrial Deformation Mechanics in a Large Asian Population Free from Clinical Heart Failure.

Non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease share several cardiometabolic risk factors. Excessive visceral fat can manifest as ectopic fat depots over vital organs, such as the heart and liver. This study assessed the associations of NAFLD and liver fibrosis with cardiac structural and functional disturbances. We assessed 2161 participants using ultrasound, and categorized them as per the NAFLD Fibrosis Score into three groups: (1) non-fatty liver; (2) fatty liver with low fibrosis score; and (3) fatty liver with high fibrosis score. Epicardial fat volume (EFV) was measured through multidetector computed tomography. All participants underwent echocardiographic study, including tissue Doppler-based E/e’ ratio and speckle tracking-based left ventricular global longitudinal strain, peak atrial longitudinal strain (PALS), and atrial longitudinal strain rates during systolic, early and late-diastolic phases (ALSRsyst, ALSRearly. ALSRlate). Larger EFV, decreased e’ velocity, PALS, ALSRsyst, and ALSRearly, along with elevated E/e’ ratio, were seen in all groups, especially in those with high fibrosis scores. After multivariate adjustment for traditional risk factors and EFV, fibrosis scores remained significantly associated with elevated E/e’ ratio, LA stiffness, and decreased PALS (β: 0.06, 1.4, −0.01, all p < 0.05). Thus, NAFLD is associated with LV diastolic dysfunction and subclinical changes in LA contractile mechanics.

IDF21-0383 Circulating GDF15 Predicted Mortality in Aging Chinese People with Type 2 Diabetes: Findings from Da Qing Diabetes Study

Background: Growth differentiation factor 15 (GDF15) is a member of the transforming growth factor-β (TGF-β) superfamily. In people with type 2 diabetes, GDF15 is elevated and related to diabetic complications, such as diabetic retinopathy, and diabetic nephropathy. While the association of GDF15 and major adverse cardiovascular events (MACE) is not significant after adjustment of cardiovascular risk factors. A Mendelian randomization study also reported that GDF15 was not associated with type 2 diabetes and coronary artery disease risk factors. Therefore, the relationship between GDF15 and cardiovascular diseases in people with type 2 diabetes still need more studies to confirm. Aim: This study aims to investigate the relationship between circulating GDF15 and mortality including all-cause, cardiovascular, and cancer death in Chinese aging people with type 2 diabetes using the long-term follow-up data of the Da Qing Diabetes Study. Method: A total of 510 subjects from the Da Qing Diabetes Study with type 2 diabetes were enrolled in the present study. The circulating GDF15 in 2006 or 2009 were assessed. Outcomes of all-cause, cardiovascular, and cancer mortality were followed in 2016 (mean follow-up of 7.5 years). Time-to-event survival curves for each outcome were created using the cumulative incidence method, and comparisons between the groups were performed with log-rank tests. Cox proportional hazards regression was used for the estimation of hazard ratios (HRs) and their 95% confidence intervals (CIs) for death. Results: At the end of the follow-up, 143 (28.0%) subjects died and 54.5% (78/143) were cardiovascular death. The cumulative incidence of all-cause death in the third tertile group was higher than that in the lowest level group (58.6% [95% CI 43.7 – 73.6] vs 19.6% [95% CI 12.7 – 26.5], log-rank p < 0.0001). Compared to the first tertile group of GDF15, the risk of all-cause death (HR = 3.27, 95% CI [1.90 – 5.64]), and cardiovascular death (HR = 3.11, 95% [1.45 – 6.67]) in the third tertile group increased more than two folds, even after adjustment of age, sex, smoking, SBP, LDL-c, HbA1c, duration of diabetes, and CVD history. Increased GDF15 level (per 1 SD increase) related to a higher risk of cancer death in all subjects (HR = 2.25, 95%CI [1.34 – 3.80]) and those without CVD (HR = 2.88, 95%CI [1.59 – 5.24]) after adjustment of traditional risk factors. Discussion: In the present study, an elevated level of GDF15 is related to the higher risk of all-cause, cardiovascular, and cancer death in Chinese aging people with type 2 diabetes. The results of all-cause and cardiovascular death were consistent regardless of CVD history. Expression of GDF15 was upregulated in response to many stimuli, and involved in cell stress, such as responding to ischemia in cultured cardiomyocytes. The substantial mechanism may be the protective role of GDF15 in the disease process, including insulin resistance regulation, anti-apoptosis, and anti-inflammation. These data provide more insight into the prevention of diabetic complications especially the primary and secondary prevention of cardiovascular death. The predictive power of GDF15 deserves more attention.

Healthful eating patterns, serum metabolite profile and risk of diabetes in a population-based prospective study of US Hispanics/Latinos.

We aimed to evaluate associations of multiple recommended dietary patterns (i.e. the alternate Mediterranean diet [aMED], the Healthy Eating Index [HEI]-2015 and the healthful Plant-based Diet Index [hPDI]) with serum metabolite profile, and to examine dietary-pattern-associated metabolites in relation to incident diabetes. We included 2842 adult participants free from diabetes, CVD and cancer during baseline recruitment of the Hispanic Community Health Study/Study of Latinos. Metabolomics profiling of fasting serum was performed using an untargeted approach. Dietary pattern scores were derived using information collected by two 24h dietary recalls. Dietary-pattern-associated metabolites were identified using multivariable survey linear regressions and their associations with incident diabetes were assessed using multivariable survey Poisson regressions with adjustment for traditional risk factors. We identified eight metabolites (mannose, γ/β-tocopherol, N1-methylinosine, pyrraline and four amino acids) that were inversely associated with all dietary scores. These metabolites were detrimentally associated with various cardiometabolic risk traits, especially insulin resistance. A score comprised of these metabolites was associated with elevated risk of diabetes (RRper SD 1.54 [95% CI 1.29, 1.83]), and this detrimental association appeared to be attenuated or eliminated by having a higher score for aMED (pinteraction = 0.0001), HEI-2015 (pinteraction = 0.020) or hPDI (pinteraction = 0.023). For example, RR (95% CI) of diabetes for each SD increment in the metabolite score was 1.99 (1.44, 2.37), 1.67 (1.17, 2.38) and 1.08 (0.86, 1.34) across the lowest to the highest tertile of aMED score, respectively. Various recommended dietary patterns were inversely related to a group of metabolites that were associated with elevated risk of diabetes. Adhering to a healthful eating pattern may attenuate or eliminate the detrimental association between metabolically unhealthy serum metabolites and risk of diabetes.

Dietary oxalate to calcium ratio and incident cardiovascular events: a 10-year follow-up among an Asian population

Background and aimThe potential cardiovascular impact of usual intakes of oxalate (Ox) is uninvestigated. We evaluated the effect of dietary Ox and its interaction with dietary calcium (Ca) on incident cardiovascular disease (CVD).MethodsWe included 2966 adult men and women aged 19–84 y without known CVD during baseline enrollment (2006–2008) of the Tehran Lipid and Glucose Study. Dietary intakes were assessed using a validated FFQ, and incident CVD (i.e., coronary heart disease, stroke, and CVD mortality) were documented through March 2018.ResultsA 7.1% incident of CVD occurred during a median follow-up of 10.6 y. After multivariable adjustment for traditional risk factors and key dietary nutrients, including total fat and fiber, Ox intakes ≥220 mg/d increased incident CVD (HR T3 vs. T1 = 1.47, 95% CI = 1.02–2.12). This association was potentiated (HR T3 vs. T1 = 2.42, 95% CI = 1.19–4.89) in subjects who had a lower intake of Ca (< 981 mg/d); in a low-Ca diet, an even lower amount of dietary Ox (second tertile, 148–220 mg/d) was related to increased CVD events by 92% (HR = 1.92, 95% CI = 1.00–3.70). No association was observed between dietary Ox and CVD events in the presence of medium- and high levels of Ca intakes. The critical cut-off point of Ox-to-Ca for predicting CVD events was 0.14, which was related to an increased risk of CVD by 37% (HR = 1.37, 95% CI = 1.02–1.84).ConclusionHigher dietary Ox intake appeared to be associated with a modestly elevated risk of incident CVD, especially in a diet with a lower amount of Ca.

Dysphagia Management and Outcomes in Elderly Stroke Patients with Malnutrition Risk: Results from Chinese Stroke Center Alliance.

PurposeTo investigate the effectiveness of dysphagia screening and subsequent swallowing rehabilitation in elderly stroke patients with malnutrition risk.Patients and MethodsBased on the Chinese Stroke Center Alliance (CSCA) from August 1, 2015 to July 21, 2019, we compared the in-hospital adverse outcomes among stroke patients (including ischemic stroke, intracranial hemorrhage, and subarachnoid hemorrhage) over 70 years old with and without dysphagia screening. The primary outcome was in-hospital all-cause mortality. Secondary outcomes were the composite endpoint of discharge against medical advice (DAMA) or in-hospital death.ResultsAmong 365,530 stroke patients ≥ 70 years old with malnutrition risk in the CSCA, documented dysphagia screening was performed for 288,764 (79.0%) participants. Of these, 41,482 (14.37%) patients had dysphagia, and 33,548 (80.87%) patients received swallowing rehabilitation. A total of 1,694 (0.46%) patients experienced in-hospital death. After adjustment for traditional risk factors, dysphagia screening was associated with a low risk of all-cause mortality in stroke patients [adjusted odds ratio (aOR): 0.75, 95% confidence interval (CI):0.65–0.87]. Compared to patients with dysphagia who did not receive swallowing rehabilitation, patients reveiving swallowing rehabilitation had a reduced risk of in-hospital death (aOR:0.39, 95% CI: 0.33–0.46). Additionally, dysphagia screening had a lower risk for the composite endpoint of DAMA or in-hospital death (aOR:0.83,95% CI: 0.80–0.87), as did subsequent swallowing rehabilitation (aOR:0.43,95% CI: 0.40–0.47). Similar results were observed in the sensitivity analysis through inverse probability of treatment weighting, propensity score matching, and excluding patients without National Institutes of Health Stroke Scale scores. A similar association was observed between dysphagia management and adverse clinical outcomes in ischemic stroke and intracranial hemorrhage patients.ConclusionDysphagia screening and swallowing rehabilitation were associated with a reduced risk of in-hospital death and composite outcome of DAMA or in-hospital death for stroke patients with malnutrition risk. Future research should concentrate on improving the quality of medical care for dysphagia management to improve patients’ outcomes.

Comparison of 24-h Urine Protein, Urine Albumin-to-Creatinine Ratio, and Protein-to-Creatinine Ratio in IgA Nephropathy.

BackgroundProteinuria is a strong risk factor for renal outcomes in IgA nephropathy. Random urine protein-to-creatinine ratio (PCR), random albumin-to-creatinine ratio (ACR), and 24-h urine protein excretion (24-h UP) have been widely used in clinical practice. However, the measurement which is the best predictor of long-term renal outcomes remains controversial. This study aimed to compare the three measurements in IgA nephropathy.MethodsWe conducted a retrospective study of 766 patients with IgA nephropathy. The associations among baseline ACR, PCR, and 24-h UP with chronic kidney disease (CKD) progression event, defined as 50% estimated glomerular filtration rate (eGFR) decline or end stage kidney disease (ESKD), were tested and compared.ResultsIn this study, ACR, PCR, and 24-h UP showed high correlation (r = 0.671–0.847, P < 0.001). After a median follow-up of 29.88 (14.65–51.65) months, 51 (6.66%) patients reached the CKD progression event. In univariate analysis, ACR performed better in predicting the prognosis of IgA nephropathy, with a higher area under the receiver operating curve (ROC) curve than PCR and 24-h UP. After adjustment for traditional risk factors, ACR was most associated with composite CKD progression event [per log-transformed ACR, hazard ratio (HR): 2.82; 95% (95% CI): 1.31–6.08; P = 0.008].ConclusionsIn IgA nephropathy, ACR, PCR, and 24-h UP had a high correlation. ACR performed better in predicting the prognosis of IgA nephropathy.

Change in Left Atrioventricular Coupling Index to Predict Incident Atrial Fibrillation: The Multi-Ethnic Study of Atherosclerosis (MESA).

Background Left atrial (LA) and left ventricular (LV) structural and functional parameters have independent prognostic values as predictors of atrial fibrillation (AF). Purpose To investigate the prognostic value of a left atrioventricular coupling index (LACI) and average annualized change in LACI (hereafter, ΔLACI) measured by cardiac MRI to predict incident AF in a population-based sample from the Multi-Ethnic Study of Atherosclerosis (MESA). Materials and Methods In a secondary analysis of the prospective MESA, 1911 study participants without clinically recognized AF and cardiovascular disease at baseline had LACI assessed with cardiac MRI at baseline (examination 1, 2000-2002) and 10 years later (examination 5, 2010-2012). LACI was defined as the ratio of LA to LV end-diastolic volumes. Univariable and multivariable Cox proportional hazard models were used to evaluate the associations of LACI and average ΔLACI with incident AF. Results Among the 1911 participants (mean age, 59 years ± 9 [standard deviation]; 907 men), 87 incident AF events occurred over 3.9 years ± 0.9 after the second imaging (examination 5). After adjustment for traditional risk factors, greater LACI and ΔLACI were independently associated with AF (hazard ratio, 1.69 [95% CI: 1.46, 1.96] and 1.71 [95% CI: 1.50, 1.94], respectively; both P < .001). Adjusted models for LACI and ΔLACI showed improvement in model discrimination compared with currently used AF risk score (Cohort for Heart and Aging Research in Genomic Epidemiology-Atrial Fibrillation, or CHARGE-AF, score) model (area under receiver operating characteristic curve [AUC], 0.78 vs 0.74; and AUC, 0.80 vs 0.74, respectively; both P < .001); and to the final model including individual LA or LV parameters for predicting AF incidence (AUC, 0.78 vs 0.76; and AUC, 0.80 vs 0.78, respectively; both P < .001). Conclusion Atrioventricular coupling (left atrioventricular coupling index [LACI]) and coupling change (annual change in LACI) were strong predictors for atrial fibrillation (AF) in a multiethnic population. Both had incremental prognostic value for predicting AF over traditional risk factors, and superior discrimination compared with the Cohort for Heart and Aging Research in Genomic Epidemiology-Atrial Fibrillation, or CHARGE-AF, score and to individual left atrial or left ventricular parameters. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Leiner in this issue.

Association of Serum β-Hydroxybutyrate and Coronary Artery Disease in an Urban Chinese Population

Ketone bodies, including β-hydroxybutyrate (BHB), acetoacetate (AA), and acetone, can substitute and alternate with glucose under conditions of fuel/food deficiency. Ketone-body metabolism is increased in a myriad of tissue-metabolism disorders. Perturbations in metabolism are major contributors to coronary artery disease (CAD). We investigated the association of BHB with CAD. A total of 2,970 people of Chinese Han ethnicity were enrolled. The Gensini score was calculated for all patients who had positive findings. The serum level of BHB and other laboratory parameters were measured. The association of serum levels of metabolites with traditionally risk factors and CAD severity was analyzed. The BHB was found to be associated with some traditional risk factors of CAD and CAD severity, as determined by the Gensini score or the number of diseased regions. Moreover, BHB was associated with the T3/T1 tertiles of the Gensini score after the adjustment for traditional risk factors by multivariable logistic regression analysis. The association of BHB with CAD severity was more obvious in women. Taken together, these data suggest that the circulating BHB level is independently associated with CAD severity, and that this association is more pronounced in women.

Intensive Systolic Blood Pressure Lowering and Kidney Disease Progression in IgA Nephropathy: A Cohort Study.

BackgroundHypertension has been shown to be an important risk factor in IgA nephropathy (IgAN). The 2021 the Kidney Disease Improving Global Outcomes (KDIGO) Guideline proposes a target systolic blood pressure (SBP) of less than 120 mmHg in patients with Chronic Kidney Disease (CKD) not receiving dialysis. However, whether lowering SBP from <140– <120 mm Hg is renoprotective is unknown. This study aims to evaluate the association of SBP and the progression of IgAN, then explore whether lowering SBP from <140– <120 mm Hg is renoprotective.MethodsOverall, 2,240 patients with IgAN were enrolled in this study. Cox proportional hazards models and restricted cubic splines were used to estimate the associations between SBP and kidney failure events which are defined as 50% estimated glomerular filtration rate (eGFR) decline or kidney failure.ResultsAfter a median follow-up of 30.05 months, 217 (9.69%) patients reached composite kidney failure events. The association of SBP and kidney failure events showed a linear relationship. The risk of kidney failure events was greater with higher SBP. Compared with SBP <120 mm Hg, the hazard ratio was 1.85 (1.16–2.97, p = 0.010) for SBP <140 mm Hg after adjustment for traditional risk factors. The renoprotective benefits of therapy targeting SBP <120 mm Hg from SBP <140 mm Hg was detectable within the subgroup with proteinuria >1.0 g/d, CKD 1-3a stage, but not those with proteinuria ≤ 1.0 g/d and CKD 3b-4 stage.ConclusionsIn patients with IgAN, SBP was independently associated with composite kidney failure events. Lowering SBP from <140– <120 mm Hg was renoprotective.

Relationship of mean platelet volume to severity of coronary atherosclerosis in non-ST-segment myocardial infarction

Abstract Funding Acknowledgements Type of funding sources: None. Background Platelets play a crucial role in thrombotic mechanism. Mean platelet volume (MPV) is primarily indicator of platelet activation and its measurement is easy and time-effective. The MPV is associated with adverse cardiac events in coronary artery disease. However, limited data are available to assess the relationship of MPV to severity of coronary atherosclerosis through multiple indicators including SYNTAX and GENSINI scores and multivessel disease (MVD) in non-ST-segment elevation myocardial infarction (NSTEMI). Objective We tested the association of MPV to severity of coronary atherosclerosis via multiple indicators in NSTEMI. Methods Ninety-three newly diagnosed NSTEMI patients (male 80.6% male and mean age 60.1 ± 12.3) were prospectively enrolled those who underwent first-time coronary angiography. The MVD defined as having stenosis &amp;gt;70% in &amp;gt;1 coronary vessels and clinical risk scores including SYNTAX and GENSINI were calculated to stratify coronary atherosclerosis severity. These indicators were sub-categorized into low risk (score &amp;lt;23) versus intermediate-high risk (score ³23) SYNTAX and GENSINI scores and MVD versus single vessel disease. The MPV was obtained from complete blood count analysis prior to coronary angiography. Results Patients with intermediate-high risk SYNTAX (P = 0.001) and GENSINI (P = 0.002) scores had higher MPV values as compared to low risk. The higher MPV was also observed in in MPV than single vessel disease (P = 0 .017). The MPV was positively correlated with SYNTAX score (r = 0.281, P = 0.006, Spearmen’s Correlation), GENSINI (r = 0.219, P = 0.035, Spearmen’s Correlation), and MVD (r = 0.243, P = 0.019, Spearmen’s Correlation). Using logistic regression analysis after adjustment of traditional risk factors, we observed MPV remained independently associated with intermediate-high risk SYNTAX [odds ratio (OR): 0.881(95% confidence interval (Cl): 0.247-1.516), P = 0.006) and GENSINI scores [OR: 0.782(95%Cl: 0.131-1.434), P = 0.019) and MVD [OR: 0.718(95%Cl: 0.027-1.409), P = 0.042]. Operating characteristic curves (AUC) for MPV also evaluated intermediate-high SYNTAX score [AUC: 0.696(95%Cl: 0.587-0.804), P = 0.001) and GENSINI score [AUC: 0.694(95%Cl: 0.062-0.851), P = 0.003] and MVD [AUC: 0.660(95% Cl: 0.541-0.779), P = 0.020]. Conclusions We studied a positive relationship of MPV with high coronary severity through multiple indicators including SYNTAX, GENSINI and MVD in NSTEMI patients.

Change in left atrioventricular coupling index to predict incident atrial fibrillation: the multi-ethnic study of atherosclerosis (MESA)

Abstract Funding Acknowledgements Type of funding sources: None. BACKGROUND Left atrial (LA) and left ventricular (LV) structural and functional parameters have independent prognostic values as predictors of atrial fibrillation (AF). PURPOSE To investigate the prognostic value of a left atrioventricular coupling index (LACI) and average annualized change in LACI measured by cardiac MRI to predict incident AF in a population-based sample from the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS In a secondary analysis of the prospective Multi-Ethnic Study of Atherosclerosis (MESA) study, 1,911 study participants, free of clinically recognized AF and cardiovascular disease at baseline, had LACI assessed with cardiac MRI at baseline (Exam 1, 2000-2002), and ten years later (Exam 5, 2010-2012). LACI was defined as the ratio of LA to LV end-diastolic volumes. Univariable and multivariable Cox proportional hazard models were used to evaluate the associations of LACI and average annualized change in LACI (ΔLACI) with incident AF. RESULTS Among the 1,911 participants (mean age 59 ± 9 years and 907 men), 87 incident AF events occurred over 3.9 ± 0.9 years following the second imaging (Exam 5). After adjustment for traditional risk factors, greater LACI and ΔLACI were independently associated with AF (HR 1.69, 95% CI[1.46-1.96] and HR 1.71, 95% CI[1.50-1.94], respectively; both p&amp;lt;.001). Adjusted models for LACI and ΔLACI showed improvement in model discrimination compared to currently used AF risk score (CHARGE-AF score) model (AUC: 0.78 vs. 0.74, and AUC: 0.80 vs. 0.74, both p&amp;lt;.001); and to the final model including individual LA or LV parameters for predicting AF incidence (AUC: 0.78 vs. 0.76, and AUC: 0.80 vs. 0.78, both p&amp;lt;.001). CONCLUSIONS Atrioventricular coupling (LACI) and coupling change (ΔLACI) were strong predictors for AF in a multi-ethnic population. Both had incremental prognostic value for predicting AF over traditional risk factors, and superior discrimination compared to the CHARGE-AF score and to individual LA or LV parameters. ClinicalTrials.gov Identifier: NCT00005487 Abstract Figure. Kaplan-Meier curves by change in LACI Abstract Figure. Kaplan-Meier curves by ΔLACI and LACI

A new marker to predict incident atrial fibrillation: Change in left atrioventricular coupling index. Report from the Multi-Ethnic Study of Atherosclerosis (MESA)

Left atrial (LA) and left ventricular (LV) structural and functional parameters have independent prognostic values as predictors of atrial fibrillation (AF). To investigate the prognostic value of a left atrioventricular coupling index (LACI) as well as change in LACI to predict incident AF in a multi-ethnic population. In the Multi-Ethnic Study of Atherosclerosis (MESA), 1911 study participants, free of clinically recognized AF and cardiovascular disease at baseline, had LACI assessed with CMR imaging at baseline (Exam 1, 2000–2002), and ten years later (Exam 5, 2010–2012). LACI was defined as the ratio of LA to LV end-diastolic volumes. Univariable and multivariable Cox proportional hazard models were used to evaluate the associations of LACI and average annualized change in LACI (ΔLACI) with incident AF. Among the 1911 participants (mean age 59 ± 9 years and 47.5% male participants), 87 incident AF events occurred over 3.9 ± 0.9 years following the second imaging (Exam 5). After adjustment for traditional risk factors, greater LACI and ΔLACI were independently associated with AF (HR: 1.69, 95% CI [1.46–1.96] and HR: 1.71, 95% CI [1.50–1.94], respectively; both P < 0.0001). Adjusted models for LACI and ΔLACI showed significant improvement in model discrimination compared to currently used AF risk score model for predicting AF incidence (C-statistic: 0.78 vs. 0.74, and C-statistic: 0.80 vs. 0.74, respectively). The LACI and ΔLACI also showed superior discrimination performance for AF compared to the multivariable model including CHARGE-AF score, and individual LA or LV parameters (Fig. 1). Atrioventricular coupling (LACI) and coupling change (ΔLACI) are strong predictors for AF incidence in a multi-ethnic population. Both have incremental prognostic value for predicting AF over traditional risk factors, and superior discrimination power compared to the CHARGE-AF score and to individual LA or LV parameters.

Change in left atrioventricular coupling index to predict hard cardiovascular disease: The Multi-Ethnic Study of Atherosclerosis (MESA)

Both left atrial (LA) and left ventricular (LV) functional parameters influence the prognosis of patients with cardiovascular diseases (CVD). This study aimed to investigate the prognostic value of a novel left atrioventricular coupling index (LACI), as well as annual change in LACI (ΔLACI) for predicting hard CVD in a population without history of CVD at baseline. In the Multi-Ethnic Study of Atherosclerosis (MESA), 2221 study participants, free of CVD at baseline, had LACI assessed with CMR imaging at baseline (Exam 1, 2000–2002), and ten years later (Exam 5, 2010–2012). LACI was defined by the ratio of the LA end-diastolic volume divided by the LV end-diastolic volume. Cox proportional hazard models were used to evaluate the associations of LACI and average annualized change in LACI (ΔLACI) with hard CVD defined by myocardial infarction, resuscitated cardiac arrest, fatal and nonfatal stroke, or CHD death. Among the 2221 participants (62.8 ± 10.1 years, 47.9% men), 223 cardiovascular events were observed (mean follow-up 13.0 ± 3.2 years). After adjustment for traditional risk factors, greater LACI and ΔLACI were independently associated with hard CVD (HR: 1.23; 95% CI [1.13–1.34] and HR: 1.71, 95% CI [1.50–1.94]; both P < 0.0001). Adjusted models for LACI and ΔLACI showed significant improvement in model discrimination compared to traditional risk score model (C-statistic: 0.79 vs. 0.77, and C-statistic: 0.80 vs. 0.78, respectively) ( Fig. 1 ). LACI is a strong predictor for the incidence of hard CVD. LACI has incremental prognostic value to predict hard CVD over traditional risk factors, and better discrimination and reclassification power compared to individual LA or LV parameters.

Growth Differentiation Factor-15 Predicts Death and Stroke Event in Outpatients With Cardiovascular Risk Factors: The J-HOP Study.

BackgroundGrowth differentiation factor‐15 (GDF‐15) has emerged as a novel biomarker to predict all‐cause death in community‐dwelling individuals and patients with cardiovascular disease. We evaluated the prognostic value of GDF‐15 in outpatients with cardiovascular risk factors.Methods and ResultsGDF‐15 levels were measured in 3562 outpatients with cardiovascular risk factors in the J‐HOP (Japan Morning Surge‐Home Blood Pressure) study, a nationwide prospective study. Participants were stratified according to tertiles of GDF‐15 and followed up for all‐cause death and cardiovascular disease. During a mean follow‐up period of 6.6 years, there were 155 all‐cause deaths, 81 stroke events including cerebral infarction and intracranial hemorrhage, and 141 cardiac events including cardiac artery disease and heart failure. Patients with higher GDF‐15 levels were associated with risks of all‐cause death and stroke events (except for cardiac events) after adjustment for traditional risk factors and other prognostic biomarkers (NT‐proBNP [N‐terminal pro‐B‐type natriuretic peptide], high‐sensitivity troponin T; all‐cause death, hazard ratio, 2.38; 95% CI, 1.26–4.48; P=0.007; stroke events, hazard ratio, 2.93; 95% CI, 1.31–6.56, P=0.009; compared with the lowest tertile). Furthermore, incorporating GDF‐15 to the predictive models for all‐cause death improved discrimination and reclassification significantly. For stroke events, GDF‐15 showed similar diagnostic accuracy to NT‐proBNP and high‐sensitivity troponin T.ConclusionsIn Japanese outpatients with cardiovascular risk factors, GDF‐15 improves risk stratification for all‐cause death when compared with NT‐proBNP and high‐sensitivity troponin T. GDF‐15 was associated with increased risks of stroke events beyond conventional risk factors and other prognostic markers; however, the predictive ability for stroke events was equivalent to NT‐proBNP and high‐sensitivity troponin T.RegistrationURL: http://www.umin.ac.jp/ctr.; Unique identifier: UMIN000000894.

Neutrophil-To-Lymphocyte Ratio and Abdominal Aortic Atherosclerosis among Asymptomatic Individuals.

ResumoFundamento A razão neutrófilo-linfócito (RNL) tem sido proposta como um marcador inflamatório possivelmente associado a aterosclerose coronariana, embora a maioria dos dados atuais seja restrita à fase aguda. Além disso, a associação entre a RNL e a aterosclerose extracoronariana ainda não está clara.Objetivo Analisar a associação entre a RNL e aterosclerose da aorta abdominal (AtAA).Métodos Foram incluídos pacientes assintomáticos submetidos a um programa de rastreamento. A AtAA foi avaliada através de ultrassom. Os números absolutos de leucócitos e linfócitos foram utilizados para calcular a RNL. Foi estabelecido um nível de significância estatística de 0,05.Resultados De 36.985 indivíduos (idade: 42±10 anos, 72% homens), foi identificada a presença de AtAA em 7%. Aqueles com AtAA eram mais velhos e tinham maior propensão a serem homens e diabéticos. A presença de AtAA foi associada a RNL aumentada (odds ratio [OR] 1,17; intervalo de confiança de 95% [IC95%] 1,13-1,21). No entanto, a associação deixou de ser significativa quando a análise foi ajustada para os fatores de risco (OR 1,02; IC95% 0,97-1,06), principalmente devido à inclusão da idade no modelo. Quando os neutrófilos e linfócitos foram analisados separadamente, a associação negativa entre os linfócitos e a RNL foi invertida com a inclusão da idade, o que sugere um forte efeito confundidor da idade na relação entre linfócitos e aterosclerose. Por fim, a associação entre os neutrófilos e a AtAA deixou de ser significativa após o ajuste adicional para os fatores de risco tradicionais, mas não apenas para a idade.Conclusão Embora a RNL tenha se associado a AtAA, foi principalmente devido ao efeito confundidor da idade. No geral, os resultados sugerem um papel limitado da contagem de leucócitos como biomarcador de AtAA.

Coronary Artery Disease Events and Carotid Intima-Media Thickness in Type 1 Diabetes in the DCCT/EDIC Cohort.

BackgroundCarotid artery intima‐media thickness (IMT) is associated with the risk of subsequent cardiovascular events in the general population. This association has not been established in type 1 diabetes.Methods and ResultsWe studied if carotid IMT is associated with the risk of a first coronary artery disease event in participants with type 1 diabetes in the EDIC (Epidemiology of Diabetes Interventions and Complications) study, the long‐term observational follow‐up of the DCCT (Diabetes Control and Complications Trial). Between 1994 and 1996, common carotid artery and internal carotid artery IMT were measured with high‐resolution ultrasound in 1309 study participants with a mean age of 35 years and diabetes duration of 13.8 years; 52% were men. Cox proportional hazards models evaluated the association of standardized common carotid artery IMT and internal carotid artery IMT with subsequent cardiovascular events over the next 17 years. Models were adjusted for age, sex, mean hemoglobin A1c levels, and traditional cardiovascular risk factors. Associations of common carotid artery IMT with subsequent CAD were significant after adjustment for imaging device, sex, and age (hazard ratio [HR], 1.23 per 0.09 mm [95% CI, [1.04–1.45]; P=0.0141), but did not remain significant after further adjustment for traditional risk factors and hemoglobin A1c (HR, 1.14 per 0.09 mm [95% CI, 0.97–1.33]; P=0.1206). No significant associations with subsequent coronary artery disease events were seen for internal carotid artery IMT.ConclusionsIn the DCCT/EDIC cohort with type 1 diabetes, common carotid artery IMT, but not internal carotid artery IMT, is weakly associated with subsequent coronary artery events, an association eliminated after adjusting for coexistent traditional cardiovascular risk factors.RegistrationURL: https://www.clinicaltrials.gov; Unique identifiers: NCT00360815 and NCT00360893.

Serum free sulfhydryl status associates with new-onset chronic kidney disease in the general population

BackgroundSerum sulfhydryl groups (R-SH, free thiols) reliably reflect the systemic redox status in health and disease. As oxidation of R-SH occurs rapidly by reactive oxygen species (ROS), oxidative stress is accompanied by reduced levels of free thiols. Oxidative stress has been implicated in the pathophysiology of chronic kidney disease (CKD), in which redox imbalance may precede the onset of CKD. Therefore, we aimed to investigate associations between serum free thiols and the risk of incident CKD as defined by renal function decline and albuminuria in a population-based cohort study. MethodsSubjects without CKD (n = 4,745) who participated in the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) study, a prospective, population-based cohort study in the Netherlands, were included. Baseline protein-adjusted serum free thiols were studied for their associations with the development of CKD, defined as a composite outcome of an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2, urinary 24-h albumin excretion (UAE) > 30 mg/24-h, or both. ResultsMedian level of protein-adjusted serum free thiols at baseline was 5.14 μmol/g of protein (interquartile range [IQR]: 4.50–5.75 μmol/g) and median eGFR was 96 mL/min/1.73 m2 [IQR: 85–106]. Protein-adjusted serum free thiols were significantly associated with incident CKD (hazard ratio [HR] per doubling 0.42 [95% confidence interval [CI]: 0.36–0.52, P < 0.001), even after adjustment for traditional risk factors (HR 0.67 [95% CI: 0.47–0.94], P=0.022). In secondary analyses, the highest tertile of protein-adjusted serum free thiols was inversely associated with incident UAE >30 mg/24-h after full adjustment for confounding factors (HR per doubling 0.70 [95% CI: 0.51–0.96], P=0.028). ConclusionHigher levels of serum R-SH, reflecting less oxidative stress, are associated with a decreased risk of developing CKD in subjects from the general population. This association is primarily driven by incident CKD as defined by UAE.